Phosphorylation of CREB Ser142 regulates light-induced phase shifts of the circadian clock

被引:216
作者
Gau, D
Lemberger, T
von Gall, C
Kretz, O
Minh, NL
Gass, P
Schmid, W
Schibler, U
Korf, HW
Schütz, G
机构
[1] German Canc Res Ctr, Div Mol Biol Cell 1, D-69120 Heidelberg, Germany
[2] Univ Geneva, Dept Mol Biol, CH-1211 Geneva, Switzerland
[3] Zent Inst Seel Gesundheit, D-68159 Mannheim, Germany
关键词
D O I
10.1016/S0896-6273(02)00656-6
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Biological rhythms are driven in mammals by a central circadian clock located in the suprachiasmatic nucleus (SCN). Light-induced phase shifting of this clock is correlated with phosphorylation of CREB at Ser133 in the SCN. Here, we characterize phosphorylation of CREB at Ser142 and describe its contribution to the entrainment of the clock. In the SCN, light and glutamate strongly induce CREB Ser142 phosphorylation. To determine the physiological relevance of phosphorylation at Ser142, we generated a mouse mutant, CREBS142A, lacking this phosphorylation site. Light-induced phase shifts of locomotion and expression of c-Fos and mPer1 in the SCN are significantly attenuated in CREBS142A mutants. Our findings provide genetic evidence that CREB Ser142 phosphorylation is involved in the entrainment of the mammalian clock and reveal a novel phosphorylation-dependent regulation of CREB activity.
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页码:245 / 252
页数:8
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